Conformal electrode arrays for electrophysiologic recording and neural stimulation within the cerebral ventricles

ABSTRACT

The present disclosure relates to an array of electrodes on a flexible scaffolding, with the ability to collapse into an axial configuration suitable for deploying through a narrow cylindrical channel. The electrode arrays can be placed into the ventricular system of the brain, constituting a minimally invasive platform for precise spatial and temporal localization of electrical activity within the brain, and precise electrical stimulation of brain tissue, to diagnose and restore function in conditions caused by abnormal electrical activity in the brain.

PRIORITY

The present application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application Ser. No. 62/395,672 filed on Sep. 16, 2016 andU.S. Provisional Application Ser. No. 62/406,623 filed on Oct. 11, 2016,the entire contents of both applications are incorporated by referenceherein.

RELATED APPLICATIONS

This application is related to U.S. application Ser. No. 15/585,746filed on May 3, 2017, entitled “A Visual Prosthesis Employing VirtualNeural Electrode Arrays”.

FIELD

The present application relates to electrophysiologic recording and/orstimulation of brain tissue using electrode arrays.

BACKGROUND

Several common disorders of the brain, spinal cord, and peripheralnervous system arise due to abnormal electrical activity in biological(neural) circuits. In general terms, these conditions may be classifiedinto:

-   -   (1) Conditions such as epilepsy, in which electrical activity is        dysregulated, and recurrent activity persists in an uncontrolled        fashion;    -   (2) Conditions such as stroke or traumatic injury, in which an        electrical pathway is disrupted, disconnecting a component of a        functional neural circuit; and    -   (3) Conditions such as Parkinson's disease, in which neurons in        a discrete region cease to function, leading to functional        impairment in the neural circuits to which they belong.

When the electrical lesion is focal and relatively discrete, as is veryoften the case, effective diagnosis and treatment of such conditionsdepends on precise localization of the lesion and, when possible,restoration of normal electrophysiologic function to the affectedregion.

A variety of well-established techniques exist for localizing electricallesions in the brain, each of which has specific limitations.

-   -   (1) Imaging techniques such as magnetic resonance imaging (MRI)        and computed tomography (CT) constitute entirely noninvasive        methods of examining brain tissue, and many functional lesions        (including strokes, anatomic abnormalities capable of causing        seizures, and foci of neuronal degeneration) can be detected and        precisely localized using such imaging modalities. Not all        functional lesions can be detected using these imaging        modalities, however, as these techniques do not image electrical        activity. Furthermore, these imaging techniques lack temporal        resolution, and provide no mechanism for therapeutic        electrophysiologic intervention.    -   (2) Electromagnetic recording techniques such as        electroencephalography (EEG) and magnetoencephalography (MEG)        are entirely noninvasive techniques that provide excellent        temporal resolution of electrical activity in the brain. For        this reason, EEG is currently the gold standard modality for        detection of seizure activity. The spatial resolution of such        techniques is limited, however, both due to physical distance of        electrodes from the brain, and by the dielectric properties of        scalp and skull. The spatial resolution of EEG is better for        superficial regions, and worse for neural activity deep within        the brain.    -   (3) Electrocorticography (ECoG), or intracranial EEG, is a form        of electroencephalography that provides improved spatial        resolution by placing recording electrodes directly on the        cortical surface of the brain (in conventional EEG, by contrast,        electrodes are positioned on the scalp). This modality is        frequently used during neurosurgical procedures to map normal        brain function and locate abnormal electrical activity, but it        requires craniotomy, temporary surgical removal of a significant        portion of the skull, in order to expose the brain surfaces of        interest, and exposes patients to the attendant risks of brain        surgery. Furthermore, while electrical activity near the        cortical surface of the brain can be mapped with reasonable        spatial resolution, electrical activity deep within the brain        remains difficult to localize using ECoG.    -   (4) “Depth electrodes” record electrical activity with high        spatial and temporal precision, but such electrodes record only        from small volumes of tissue (small populations of neurons), and        their placement requires disruption of normal brain tissue along        the trajectory of the electrode, resulting in irreversible        damage or destruction of some neurons. As such electrodes are        placed surgically, in a hypothesis-driven manner, the number of        such electrodes that can be safely placed simultaneously is        limited.    -   (5) Deep brain stimulation (DBS) electrodes, the stimulating        analog of recording depth electrodes, electrically stimulate        brain regions with millimetric precision. They are implanted        using minimally invasive surgical techniques, and can be        effective in conditions such as Parkinson's disease, in which        neuronal dysfunction is confined to a small, discrete, and        unambiguous region of the brain.

While the foregoing list is not exhaustive, it provides a generaloverview of the range of techniques presently available for electricalrecording and stimulation of the living human brain.

In practice, all neural recording and stimulation techniques involvedesign trade-offs among a number of primary factors:

-   -   (1) Spatial resolution;    -   (2) Temporal resolution;    -   (3) Degree of invasiveness; and    -   (4) Optimization for electrical recording or electrical        stimulation.

SUMMARY

An ideal electrophysiologic neural probe, should simultaneously provideoptimal performance in all four of the above categories. Exemplaryexisting solutions for lesions of particular types, in particular brainregions are as follows:

-   -   (1) Seizures arising from anatomic abnormalities near the        cortical surface are well localized by EEG and MEG.    -   (2) Symptoms of Parkinson's disease, arising from degeneration        of dopamine-producing neurons in a well-defined region (the        substantia nigra), can often be effectively modulated by precise        stimulation of a millimetric nucleus (the subthalamic nucleus)        using a small number of deep brain stimulation (DBS) electrodes.

Diagnosis and treatment of functional electrophysiologic lesions inbrain regions remain challenging or intractable. In particular, deepbrain regions are frequent sites of functional lesions, yet remaindifficult to access systematically and minimally invasively. Forexample, the medical temporal lobe is a common site for seizure foci andthe substantia nigra is the site of neuronal degeneration causingParkinson's disease; both regions are several centimeters deep to thecortical surface.

The present application discloses an electrode array for neuralrecording and stimulation, which can be deployed using minimallyinvasive techniques, to electrophysiologically localize and stimulatetargets within wide regions deep within the brain.

In one aspect, the present application discloses an implantable medicaldevice with a flexible substrate, an array of electrodes mounted on theflexible substrate for recording and stimulating neurological activitieswithin ventricles of a brain, and a conformal scaffolding supporting theflexible substrate.

In some embodiments, the array of electrodes can be periodic. In someembodiments, the conformal scaffolding can be continuous. In someembodiments, the conformal scaffolding can be a plurality of flat panelsoriented parallel to each other, and a continuous loop of metal wire,wound in a helical pattern across the plurality of parallel panels andlongitudinally along the length of the plurality of parallel panels. Insome embodiments, the metal wire can be made of a shape memory alloy,such as nitinol. In a some embodiments, the flexible substrate can be aflexible printed circuit board made of polyimide. In some embodiments,the plurality of electrodes can be made of platinum, iridium, or gold.In some embodiments, the implantable medical device further includes apower source and a microprocessor, each electrically coupled to thearray of electrodes.

In another aspect, the present application discloses a method forelectrically interacting with a neural tissue using an electrode arraylocated within a ventricular compartment of a brain, the method caninclude selecting a portion of neural tissue for electrical interaction,accessing previously stored registration information regarding alocation of the electrode array within the ventricular compartment ofthe brain, selecting one or more electrodes in the electrode array forelectrical interaction based on the registration information, andinteracting with the neural tissue with the selected electrodes.

In some embodiments, the method can include stimulating neuralactivities of the neural tissue, or recording neural activities of theneural tissue, or simultaneously stimulating and recording neuralactivities of the neural tissue. In some embodiments, the method caninclude forming an electrical field beam distributed in athree-dimensional space using the selected electrodes. In someembodiments, the method can include localizing electrical activity inthe brain using the selected electrode distributed in athree-dimensional space. In some embodiments, the method can includelocalizing electrical activities from epileptogenic foci within ahippocampus for the management of epilepsy. In some embodiments, themethod can include stimulating the brain in response to epileptogenicactivity within the hippocampus for the management of epilepsy. In someembodiments, the method can include interacting with motor pathways byan electrical field generated by the electrode array at a distance toassist in restoring mobility and limb control. In some embodiments, themethod can include stimulating visual pathways to generate visualperception. In some embodiments, the method can include stimulatingsensory cortex or sensory thalamus to deliver sensory stimulation to thebrain for a neurosensory prosthesis or for the treatment of thalamicpain. In some embodiments, the method can include stimulatinghypothalamic nuclei for the management of neuroendocrine disorders,circadian rhythm disorders, physiologic response to fever orhypothermia, or obesity. In some embodiments, the method can includeregistering the electrode array to obtain its orientation and positionwithin the ventricular compartment of a brain via neuroimaging. In someembodiments, the method can include placing the electrode array into theventricular compartment of a brain via a minimally invasive insertiontechnique, such as a cannula or catheter.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 depicts a cross-section drawing illustrating several anatomicstructures within the human brain, and their positions with respect tothe cerebral ventricles;

FIGS. 2A-2D depict the unfolded views of a conformal intraventricularelectrode array, in accordance with embodiments of the presentdisclosure;

FIGS. 3A-3B depict the folded views of a conformal intraventricularelectrode array, in accordance with embodiments of the presentdisclosure;

FIGS. 4A-4D depict the formation of electrical fields using a singleelectrode tip, a one-dimensional linear electrode array, atwo-dimensional electrode array, and a three-dimensional electrodearray, according some embodiments of the present disclosure;

FIG. 5 depicts a flow chart of recording/stimulating electricalactivities of the brain tissue using the conformal electrode arrays inthe present disclosure;

FIGS. 6A-6C depict endoscopic insertion of a conformal electrode arrayinto the temporal horn of the right lateral ventricle in a humanpatient, in accordance with embodiments of the present disclosure;

FIG. 7 depicts a mechanical packaging of one conformal electrode array,in accordance with embodiments of the present disclosure;

FIGS. 8A-8B depict a conformal electrode array implanted in the temporalhorn of the left lateral ventricle, in accordance with embodiments ofthe present disclosure; and

FIG. 9 depicts detection of epileptogenic electrical activity within thehippocampus by a conformal array of electrodes, in accordance withembodiments of the present disclosure.

DESCRIPTION

The device described herein can be used with minimally invasivetechniques for precise spatial and temporal localization of electricalactivity within the brain, and for precise electrical stimulation ofbrain tissue, to diagnose and restore function in conditions caused byabnormal electrical activity in the brain.

An exemplary electrophysiologic neural probe provides maximal spatialand temporal resolution, enables three dimensional electrical recordingand stimulation, and can be deployed noninvasively, without disruptingnormal brain tissue.

In particular, the present disclosure describes a flexible andcollapsible array of electrodes, and a minimally invasive method ofdelivering such an array into the cerebral ventricles, the fluid-filledcavities at the center of the brain. The walls of the cerebralventricles are formed by the inner surfaces of several deep brainstructures that are difficult to access from the cortical surface,including the hippocampus and medial temporal lobe (frequently involvedin seizure disorders), the hypothalamus (which is involved in hormonalregulation, circadian rhythm, and the modulation of cravings related toa range of factors, including sleep, food, salt and water, warmth, andsex), the thalamus and basal ganglia (involved in movement disorderssuch as Parkinson's disease), and the internal capsule (frequentlydamaged in hemorrhagic stroke). By arraying electrodes along the innerwalls of the cerebral ventricles, deep brain targets can be accessedelectrically for precise electrical recording and stimulation.

In summary, electrode arrays positioned within the ventricles caninterface with structures deep within the brain, without traumatizingbrain tissue, in ways that conventional depth electrodes and surfaceelectrodes cannot. The ability of these electrodes to more extensivelyinterface with deep brain structures is due to two principal properties.First, during initial placement, ventricular arrays can be navigatedwithin a purely fluidic compartment that provides extensive access todeep brain structures. By navigating within this fluidic compartment(the cerebral ventricular system), ventricular electrode arrays avoidtraumatizing delicate brain tissue. Second, multiple neural structuresthat are difficult to access electrically using conventional techniquesare situated in close proximity to the surface of the ventricularsystem. The ventricular system of the brain can be accessed andnavigated using techniques of minimally invasive neurosurgery, includingneuro-endoscopy.

FIG. 1 is a cross-section drawing illustrating several anatomicstructures within a human brain, and their positions with respect to thecerebral ventricles. FIG. 1 includes left lateral ventricle 101,occipital horn 102, atrium 103, temporal horn 104, the third ventricle105, the left foramen of Monro 106, the right fornix 107, the leftinternal capsule 108, and the right caudate nucleus 109. There isapproximate macroscopic symmetry with respect to the vertical midline(sagittal) plane, so that left lateral ventricle 101 has a mirror imageright lateral ventricle (not shown FIG. 1), the right fornix 107 has amirror image left fornix (not shown in FIG. 1), the left internalcapsule 108 has a mirror image right internal capsule, and the rightcaudate nucleus 109 has a mirror image left caudate nucleus (not shownin FIG. 1). Labeled regions of the right lateral ventricle are occipitalhorn 102, atrium 103, and temporal horn 104. The third ventricle 105 iscontiguous with the left and right lateral ventricles through the leftforamen of Monro 106, and its mirror image right foramen of Monro (notshown in FIG. 1).

Conformal electrode arrays can be clinically useful in mapping andtargeted ablation of cardiac lesions causing heart arrhythmias. Forexample, conformal electrode arrays can be used for electrophysiologicmapping in real-time in the heart. Exemplary techniques for treatingconditions such as atrial fibrillation can use conformal electrodearrays, delivered through the major blood vessels, to record from theelectrical system of the heart (De Ponti et al. (2004) Europace6:97-108); (Yamada (2007) Indian Pacing Electrophysiol. J. 7:97-109).However, there is extremely limited precedent for intraventricularelectrode recording in the brain (Konrad et al. (2003) J. Neurol.Neurosurg. Psychiatry 74:561-565), and prior work has been conductedonly with linear electrode configurations, not with conformal arrays.Additionally, there is limited precedent for stimulation of brainregions surrounding the ventricles from within the ventricles, (Benabidet al. (2016) Neurosurgery 79:806-815) and prior work has been limitedto conventional deep brain stimulation electrodes, not conformalelectrode arrays.

FIGS. 2A-2D depict a series of unfolded views of layers of a conformalintraventricular electrode array 200, in accordance with embodiments ofthe present disclosure. FIG. 2A depicts a skeleton member 201 of aconformal electrode array in its unfolded configuration according to oneembodiment of the present disclosure. Skeleton member 201 can providethe capability of folding/unfolding of the conformal electrode array200. Skeleton member 201 can be configured to form an array of loops,for example, one loop, two loops, three loops, four loops, five loops,six loops, seven loops, eight loops, nine or more loops wide. In theembodiment depicted in FIG. 2A, skeleton member 201 can be configured toform three loops. In some embodiments, skeleton member 201 can be madeof a resilient inert metal material such as, for example, a shape memoryalloy nitinol metal or stainless steel. In some embodiments, skeletonmember 201 can composed of a shape-memory material, such as nitinol. Forexample, in some embodiments, skeleton member 201 can be Grade 1Nitinol. In some embodiments, skeleton member 201 can be about 100micrometers to about 200 micrometers, for example, 150 micrometers indiameter. In some embodiments, skeleton member 201 can be formed bywinding and training a single strand on a mandrel.

In some embodiments, array 200 can include a mechanism for expandingskeleton member 201 from the axial configuration used for initialimplantation, to an expanded, deployed configuration that conforms(based on measurements obtained, for example, from patient-specificmedical imaging) to the inner shape of the intracranial ventricularcompartment. Certain general geometric characteristics are appropriatefor implantation within the cerebral ventricles, but shape-memorymaterials permit skeleton member 201 to be sized and shaped in apatient-specific manner. Ovoid and cylindrical shapes provide usefulapproximations to the shapes of certain parts of the cerebralventricular system.

FIG. 2B depicts another view of conformal array 200. FIG. 2B includesskeleton member 201, side panels 202, a center panel 203, a stiffener204, and lead wires 206. The loops formed by skeleton member 201 allowplacement of panels 202, 203 and stiffener 204 on top of center panel203 through the loops of skeleton member 201.

In some embodiments, panels 202, 203 can be composed of polyimide orother polymer substrates suitable for fabricating flexible printedcircuits. The panels are typically rectangular, but deformable.Typically they measure between about 5 mm and about 50 mm in width,about 20 mm and about 60 mm in length, and about 10 micrometers to about100 micrometers in thickness.

A non-exclusive list of materials that can be used to make stiffener 204includes polyimide, polyether ether ketone (PEEK), polycarbonates,polyamides, polyethylene, polypropylene, polyesters, andpolyethersulfones. The stiffness of stiffener 204 can be controlled suchthat it is rigid enough to hold the array in place while it is beingunsheathed from a cannula, while stiffener 204 can be flexible enough toconform in a gentle arc per the anatomy inside the cerebral ventricles.

In some embodiments of the present disclosure, stiffener 204 and centerpanel 203 can be bonded together with a biocompatible adhesive.Exemplary biocompatible adhesives can include, but not limited to,medical grade epoxies, including flexible and high-bond-strengthcyanoacrylate epoxies. In some embodiments, stiffener 204 and centerpanel 203 can be bonded by heat curing under pressure. In someembodiments, stiffener can be molded or etched with trenches, which canbe used to hold skeleton member 201 in place. In one embodiment of thepresent disclosure, the side panels do not have stiffeners, and can wrapupwards to conform to the anatomy. In some embodiments, each side panel202 also can have a stiffener.

FIG. 2C depicts conformal electrode array 200 according to someembodiments of the present disclosure. Conformal electrode array 200 caninclude flexible printed circuit board 207, electrodes 208, conductortraces 205 and bundled lead wires 206 connected to conductor traces 205.

Flexible printed circuit board 207 can be a polymer substrate upon whicha series of electronic devices, for example, electrodes 208, can bemounted. In some embodiments, flexible printed circuit board 207 can bepolyimide, PEEK, polyacrylic, epoxy, fluoropolymers or a transparentconductive polyester film. Flexible circuit 207 can be mounted on top ofskeleton member 201 (not shown in FIG. 2C).

In order to generate a strong and focused electrical field forstimulation and recording or neural activity, flexible printed circuitboard 207 can have a periodic array of electrodes 208. For example, atotal of 350 electrodes 208 are shown in FIG. 2C, with 10 electrodes 208along the traverse side of the array 200 and 35 electrodes 208 on thelongitudinal side of the array 200. Possible electrode configurationsinclude, but are not limited to, hexagonal lattices and square lattices,as well as nonperiodic and quasiperiodic arrangements. While a periodicarray of electrodes 208 is shown, the array need not be periodic and canbe any number or configuration of electrodes necessary for the treatmentrequired. In addition, the electrodes need not be uniform in size orshape across the array, and between-electrode spacing can also varyacross the array. Possible electrode shapes include but are not limitedto circular, square, polygonal, or polygonal with rounded edges.Electrode diameters typically range from about 5 micrometers to about500 micrometers in diameter, though both larger and smaller electrodesizes are possible.

In some embodiments, flexible circuit 207 can be a continuous sheet. Insome embodiments, flexible circuit 207 can be slit by laser excision toform center and side panels to allow easier folding of conformableelectrode array 200. In the slit configuration, the electricalcomponents can be positioned such that no electrical components spanacross the fold line.

In some embodiments, electrodes 208 can be composed of a biocompatibleand electrically conducting material. Electrodes can be made ofmaterials including, but not limited to, platinum, iridium, or gold.Electrodes 208 also can be further coated with platinum-iridium or goldto improve conduction properties, biocompatibility, and radiopacity.

In some embodiments, the array of electrodes 208 supported on flexibleprinted circuit board 207 can be used for recording of electricalsignals generated by the brain in the regions surrounding the cerebralventricles, or for electrically stimulating regions of the brainsurrounding the cerebral ventricles. In some embodiments, electrodes 208in the array can be designed and arranged for recording, stimulation, orboth. Material and geometric considerations, as well as electricalimpedance considerations, apply to optimizing for one mode of operationor the other. Arrays can be configured with recording electrodes alone,stimulation electrodes alone, a combination of types, or electrodescapable of operating in both modes. Electrode surfaces can be treated,for example through chemical etching or other roughening techniques, orthrough polymer coating, to optimize their effective surface area andmodify their impedance for recording or stimulation.

In some embodiments, each electrode 208 can have an associated conductortrace 205. In some embodiments, conductor traces 205 can be used toconnect electrodes 208 to recording, stimulation, and othercomputational apparatus outside the ventricular system. Conductor traces205 can be aligned inside the loops of skeleton member 201, which can bethreaded inside the loop and merge into a single signal cable 206. Cable206 can exit the ventricular system and the skull along the insertionpath of the endoscope used to implant the array, as discussed below. Insome embodiments, conductor traces 205 can be composed of any suitablebiocompatible conductor, for example, gold. In some embodiments,conductor traces 205 can be gold at nine micrometers thick, sandwichedinside flexible printed circuit board 207. Cable 206 can pass through anarrow-diameter tract through the cerebral cortex and cortical whitematter, to exit through a small burr hole surgically drilled through theskull at the time of initial implantation. Accordingly, and as discussedin detail below, electrode array 200 can be connected to an implantablepower source, implanted microcomputer, and implanted mechanism for datatelemetry and communication with external devices. In some embodiments,the power source and microcomputer can be external to the body.

In some embodiments, a biocompatible coating can be conformal coated onto the entire assembly as a moisture barrier and lubricating coating. Insome embodiments, the entire assembly can be conformally coated withParylene C.

FIG. 2D shows an axial cross section of the conformal electrode array inan unfolded configuration according to an embodiment of the presentdisclosure. Corresponding to the perspective view in FIG. 2C, FIG. 2Dincludes skeleton member 201, side panel 202, center panel 203,stiffener 204, flexible printed circuit board 207, and electrodes 208.This view also depicts that each panel 203, 202 is located in individualloops of skeleton member 201. Bold line 209 of the skeleton member 201indicates its helical nature along the longitudinal axis of the device200. The distribution of ten electrodes 208 on the traverse side of theelectrode array is also shown in this cross section view, with fourelectrodes mounted on the flexible circuit 207 on central panel 203, andthree electrodes mounted on the flexible printed circuit board 207 oneach side panel 202. Each line of the ten electrodes 208 is periodicallyaligned along the longitudinal side of the device 200. Many other arrayconfigurations are envisioned, as described above, as the total numberof electrodes, their sizes, and the inter-electrode spacing can bevaried. In particular, by reducing electrode size and electrode spacing,conformal arrays can be manufactured with large numbers of electrodes.For example, 10 micrometer diameter electrodes spaced at aninter-electrode spacing of 10 micrometers in a square lattice results inan array of 250,000 electrodes per square centimeter, or 1 millionelectrodes per four square centimeters of array surface area. In someembodiments, the electrodes can be about 20 micrometers in diameter andspaced at 20 micrometers. Generally, the inter-electrode spacing can beabout one half the diameter of a neuron.

FIG. 3A (cross-section view) and FIG. 3B (perspective view) depict afolded configuration of conformal electrode array 200 according to anembodiment of the present disclosure. This folded configuration allowselectrode array 200 to accommodate cannulation prior to deployment. FIG.3A includes skeleton member 201, center panel 203, side panel 202,flexible printed circuit board 207, and electrode contacts 208. Theflexible mechanical structure can collapse into a narrow, axialconfiguration. In the embodiment depicted in FIG. 3A, with three loopsin skeleton member 201, the three loops with two side panels 202 andcenter panel 203 collapse into a triangular shape. The associatedflexible printed circuit board 207 and electrodes 208 are alsodistributed on the sides of the triangular scaffold accordingly.

The collapsed configuration of the electrode array 200, as shown in theperspective view in FIG. 3B, is suitable for minimally invasive surgicaldeployment through a narrow cylindrical channel, with precision guidancefrom neuroimaging and under direct endoscopic visualization. In someembodiments, the narrow cylindrical channel can be less than twomillimeters in width, such as the working channel of a standardneurosurgical endoscope. The present disclosure further includes amechanism for converting electrode array 200 between the axial anddeployed configurations. The conformal electrode array assumes a foldedaxial configuration inside the cylindrical channel to be transportedinto the implantation site inside the ventricle. The forward transitionfrom axial to deployed is required during initial implantation. Thereverse transition from deployed to axial is required for removal of theelectrode array. During the reverse transition, a retraction force isapplied through cable 206, the opening of the cylindrical channelcompresses electrode array 200, the compression causes folding of array200 into an axial configuration, which allows it to be removed from theimplantation site back into the cylindrical channel.

In some embodiments, skeleton member 201 can be calibrated in apatient-specific manner to exert adequate pressure on the walls of theventricular compartment to remain in fixed position and in contact withthe inner ventricular surface, but without disrupting neurologicfunction and without significantly deforming the anatomic structuresforming the boundaries of the ventricular compartment. In someembodiments, the contact pressure may be almost negligible, for example,just adequate to maintain the skeleton member 201 in the shape of thecavity, without exerting a physiologically significant pressure on thesurrounding brain. The very minimal residual pressure can beaccommodated over time by the brain with negligible clinical physiologiceffect.

Prior neural electrical stimulation techniques have been one-dimensionalor two-dimensional in nature. For example, some techniques for neuralstimulation in the context of electrode arrays have been demonstrated inthe context of interleaved stimulation and current steering techniquesfor cochlear implants (Rubenstein (2004) Curr. Opin. Otolaryngol. HeadNeck Surg. 5:444-448); (Choi et al. (2012) Cochlear Implant ResearchUpdates, Chapter 5). The electrode arrays and neural substrates ofinterest in cochlear implant applications, however, are essentiallyone-dimensional. Recent developments in the context of deep brainstimulation (Timmermann et al. (2015) Lancet Neurol. 14:693-701) havedemonstrated the value of current-steering techniques in deep brainstimulation, but those systems are also limited by being essentiallyone-dimensional as well. This revised approach to deep brainstimulation, using multiple current-sources, has recently been describedand implemented (Timmermann et al. (2015) Lancet Neurol. 14:693-701),but the approach, while effective, remains limited in the sense that theelectrode array is effectively linear, and requires intraparenchymalplacement. The volume of brain tissue accessible for neural stimulationusing deep brain simulation electrodes is extremely limited as comparedwith the planar intraventricular electrode arrays described here, whichcan assume three-dimensional shapes. Additionally, the deep brainstimulation electrodes must penetrate deep into the brain, damagingneural tissue along the insertion tract. The device disclosed hereinrelates to three-dimensional conformal electrode arrays, used to recordfrom or stimulate three-dimensional volumes of neural tissue, which hasnot been accomplished by the prior art techniques.

An electrode array on a three-dimensional surface enables more versatileshaping of electric fields and more precise spatial targeting thanconventional one-dimensional and two-dimensional electrode arrays. Theability to position arrays of many electrodes deep within the brainconfers such arrays the further ability to generate tailored electricalfields, designed to stimulate an individual brain region with highspatial and temporal precision. In contrast to depth electrodes (such asthose used in deep brain stimulation), for which intraparenchymalposition is the primary determinant of the region stimulated, theregions accessible to stimulation by conformal arrays can be programmedwith many degrees of freedom after deployment. Accordingly, stimulationby the described conformal electrode array does not require the directproximity to the region of interest as does stimulation by linear depthelectrodes such as those used in deep brain stimulation.

Because of the high volumetric density of neurons within the brain,focused electrical fields are required for effective and precise neuralstimulation. In some embodiments, a beam-formed electrical field can becreated by the stimulation device. This can require three-dimensionaldistribution of the electrode contacts inside the brain. The conformablearray described in the present disclosure with three-dimensionaldistribution of electrodes enables beam forming of the electrical field.Beam formation enables a strong and focused stimulation of brain tissue,which is an advantage over existing technologies using one-dimensionalelectrodes. Further, the relatively large number of electrodes and theconformal design of the device enable a stimulation of three-dimensionalvolumes of neural tissue.

FIGS. 4A-4D depict the formation of electrical fields using a singleelectrode tip, a one-dimensional linear electrode array, atwo-dimensional electrode array, and a three-dimensional electrodearray, according to one embodiment of the present disclosure. FIGS.4A-4D depict a single tip electrode 401, an omnidirectional(approximately isotropic) electric field with a spherical wavefront 402,a one-dimensional linear electrode array 403, a net electric field witha conical wavefront 404, a two-dimensional electrode array 405, a groupof neurons and an associated bundle of axons 406, a three-dimensionalelectrode array 200 according to the present disclosure, and a singleaxon 407 stimulated by the three-dimensional electrode array.

FIG. 4A shows a probe with a single electrode tip 401 that emits anomnidirectional electric field with a spherical wavefront 402. However,a single electrode cannot pinpoint direction when sensing a voltage.FIG. 4B shows a probe with a linear array of electrodes 403 that caneither act as a series of individual point sources, or beam-form todirect a net electric field along an axis with a conical wavefront 404.Likewise, the linear array is only able to localize an incoming signalas originating from somewhere within a cone. FIG. 4C illustrates atwo-dimensional array 405 directly in contact with a planar tissuesurface containing neurons or electrically active cells, such as theretina or cerebral cortex. The axons 406 of these cells are alsodiagrammed. The array can stimulate small groups with which individualselectrodes are in contact. FIG. 4D illustrates a three-dimensional array200 with a high density of electrode contacts according to the presentdisclosure. The flat array conforms to fit in a complexthree-dimensional shape. The high-density electrode array beamforms inthree dimensions to form a high-density electric field within a regionsmall enough to stimulate specific neurons or groups of neighboringneurons. Likewise, when used as a sensor, the array is able to localizevoltage sources precisely in three-dimensional space.

Several minimally invasive approaches can be used in contemporaryneurosurgery for precise placement of devices within the cerebralventricular system. (Mark M. Souweidane. IntraventricularNeuroendoscopy: A Practical Atlas. B. Braun, Aesculap Neurosurgery,Berlin) The conformal electrode array described herein is designed tointegrate with several such techniques.

FIG. 5 is a flow chart describing a method 500 for recording/stimulatingthe electrical activities within the brain, in accordance with anembodiment of the present disclosure. The first step in implantation ofthe electrode array is to cannulate the ventricular system 502 along atrajectory suitable for deployment of the array. The cannulation may beaccomplished with a catheter alone, or with a ventricularneuroendoscope. Once the ventricular system has been cannulated, thearray may be deployed 504 using fluoroscopic guidance, using itsradio-opaque markers to guide positioning adjustments and finaldeployment position in real time. Alternatively, the array may bedeployed under direct neuroendoscopic visualization.

Following deployment, the conformal electrode array changes from acollapsed state (as shown in FIGS. 3A-3B) to an unfolded configuration(as shown in FIGS. 2A-2D). The electrode array maintains contact withthe ventricular surface, by exerting gentle pressure against theopposite wall of the ventricle. Portions of the electrode array may bemade from a shape memory alloy, such as nitinol, and its preferredconfiguration assists in unfolding the array once it is deployed from(and no longer radially confined by) the channel of the cannulation.

Following array implantation is registration of the array 506. Duringthis step, three-dimensional neuroimaging can be used to establish thefinal, deployed, spatial and anatomic orientation of an array within theventricular system. In some embodiments, elements of the conformalelectrode arrays are radio-opaque, enabling unambiguous localization ofeach electrode in three-dimensional space and with respect toneighboring neuroanatomic structures using conventional neuroimagingmodalities, such as computed tomography (CT). Registration can allow forprecise stimulation and recording of neural tissue.

After deployment, as particular electrodes transmit electrical signalsreflecting neuronal activity within the brain, it may be important inmany applications to correlate the precise positions of implantedelectrodes with their positions in three-dimensional space and withrespect to anatomic structures. Such correlations can be establishedusing CT imaging of the brain, provided the position of each electrodecan be identified on CT. For this reason, to ensure detectability via CTand fluoroscopic imaging, certain components of the electrodes and thedevice are radio-opaque. For example, in some embodiments, radioopaqueness can be achieved using platinum titanium alloys. Analysis ofsuch imaging data (typically high-resolution computed tomography, CT)forms the basis of the following:

-   -   (1) Computational determination of the anatomic origin of        recorded electrical activity (in recording mode), and    -   (2) Computational structuring of the electrical fields generated        by the array. After implantation, once the geometry of the        deployed array is established, the net electrical field, and the        resulting net current density function, is defined by the set of        current and voltage settings assigned to the electrodes in the        array.

Following registration, conformal electrode array can operate in aplurality of modes. For example, the device can operate in a recordingmode 508, a stimulation mode 512 and a feedback mode 510.

In some embodiments, the device can include a recording mode. In therecording mode, a method of correlating imaging determining the positionof the array relative to anatomic structures, with electrophysiologicrecording data from which particular neural signals arise, to determinethe spatial and neuroanatomic origin of those signals can be performed.

In some embodiments, the method can include a stimulation mode. In thestimulation mode, a method of correlating imaging determining theposition of the array relative to anatomic structures, withcomputationally determined electric field geometry, so as to achieveprecise image-guided electrical stimulation of neural structures can beperformed. In some embodiments, this method can include a method ofshaping the electric fields generated by the electrodes, so as tostimulate precise anatomic regions surrounding the cerebral ventricle;this configuration may be programmed prior to or following arrayimplantation (based on patient-specific imaging, electrode recordings,behavior, response to therapy, or other data). A set of computationalmodels, taking into account patient-specific anatomy based onneuroimaging obtained with the array in place, can be used to computethe anatomic origin of particular electrical signals recorded by thearray. Similarly, a related set of such models can be used to shape theelectrical fields and steer the electrical currents collectivelygenerated by the array within surrounding neural tissue, in order tostimulate with anatomic and functional precision.

In some embodiments, in a feedback mode, electrical stimulation andrecording can be performed simultaneously (by designating certainelectrodes for stimulation and others for recording) or in aninterleaved manner, in order to confirm efficacy of electricalstimulation in real-time, and in order to adapt electrical stimulationprograms to real-time electrophysiologic responses. In some embodiments,the device can switch between modes after implantation. Each individualelectrode in the array can be independently controlled. Once theelectrode is implanted its geometric configuration and impedance arefixed. But any electrode can theoretically be used at any time forrecording or stimulation. In practice, arrays can be fabricated withspecific electrodes designed either for recording or for stimulation,and the mode will rarely be changed after implantation. However, thecurrent or voltage settings at each stimulation electrode can beindependently controlled, as can stimulation timing; frequency,amplitude, and pulse-width of stimulation; and stimulation pulse shape,among other parameters.

The described conformal electrode array positioned in the cerebralventricles can be minimally disruptive to normal brain tissue but canhave extensive access to deep brain nuclei and fiber tracts that areotherwise difficult to access. Accordingly, the conformal array ofventricular neural electrodes disclosed herein has several majoradvantages over existing technologies.

-   -   (1) The electrodes do not damage normal brain tissue. In analogy        to cortical surface (ECoG) electrodes, the described conformal        electrode array lines the inner surface of the ventricular        system, without penetrating brain tissue. By contrast,        conventional approaches to recording and stimulation deep within        the brain has required placement of depth electrodes that damage        normal brain tissue along the insertion trajectory.    -   (2) The electrodes in the described conformal array gain        extensive, high-resolution access to large regions deep within        the brain that are difficult to access except with a small        number of depth electrodes, each of which is limited to        recording from or stimulating a small volume.

FIGS. 6A-6C depict a deployed conformal intraventricular electrode arrayusing a cannula, in accordance with embodiments of the presentdisclosure. FIGS. 6A-6D depicts cannula 601, conformal electrode array200, and temporal horn 104 of the human brain. In particular, FIGS.6A-6D illustrates endoscopic insertion of a conformal electrode arrayinto the temporal horn of the right lateral ventricle of the brain in ahuman patient. An endoscope is used to gain access to the temporal hornin minimally invasive fashion. Specifically, FIG. 6C depicts across-section of a patient with deployed conformal intraventricularelectrode array in a sagittal view (from the left), FIG. 6A depicts anexploded view of FIG. 6C, FIG. 6B depicts an axial view (from the top).Array 200 assumes a narrow axial configuration when confined to theinner channel of the cannula 601, then expands when unsheathed from thecannula 601 in the temporal horn 104 of the lateral ventricle.

FIG. 7 illustrates packaging of the conformal electrode array designedfor insertion in the temporal horn of the lateral ventricle, and forelectrical recording from the hippocampus from within the temporal horn.FIG. 7 includes electrode contacts 208, flexible substrate 701,scaffolding 702, bundled lead wires 206 as a connector, and hermeticallysealed package 703. The scaffolding can be composed of skeleton member201, side panels 202, center panel 203, and stiffener 204 (as shown inFIGS. 2A-2D). The flexible substrate can be composed of flexible printedcircuit board 207 mounted on the scaffolding. Substrate 701 is supportedby scaffolding 702 that ensures the electrode array maintains contactwith the ventricular surface, by exerting gentle pressure on theopposite wall of the ventricle. Bundled lead wires 206 exit theventricular system and the skull along the insertion path of theendoscope, and enters hermetically sealed package 703. Package 703 maybe constructed entirely from silicone, and implanted between skull andscalp. The configuration and implantation technique for this package aresimilar to those of an Ommaya reservoir, known in the neurosurgical artand commonly used for the delivery of chemotherapy in neuro-oncology.This package contains implantable electronic elements for neural signalrecording and wireless transmission.

As the leads from the recording electrodes exit the brain, they form abundle that is tunneled through a small-diameter hole surgically drilledin the skull. After exiting the skull, this bundle may be tunneled in asubcutaneous layer to a microcomputer or other device designed to powerthe electrodes, store recording data, store stimulation parameters, andcoordinate wireless data telemetry with external devices. These activeelectronic components are contained within the hermetic package. In sucha configuration, the conformal electrode array permits long-termelectroencephalographic monitoring of patients in the ambulatorysetting, as there is no fluidic communication between the brain and theoutside world, and hence no major risk of intracranial infection. Inthis configuration, the monitoring capabilities of the conformal,minimally invasive system disclosed here offer an option not availableusing conventional grid and strip electrodes, which are implanted viacraniotomy, tunneled through dura, skull, and skin, and permit leakageof cerebrospinal fluid and a conduit between the brain and the outsideworld. Epilepsy patients undergoing monitoring using such techniques,which represent the present state of the art, must be monitored in ahospital setting until the recording electrodes are removed.Furthermore, in the current state of the art, removal of the electrodesrequires a second operation for electrode removal, repair of the duramembrane, and reaffixing of the removed portion of the skull.

On the other hand, the system disclosed herein does not precludemonitoring using such conventional techniques. Using the systemdisclosed herein, device leads may also, temporarily, be tunneledthrough the skin for patient monitoring in a conventional epilepsymonitoring unit.

FIG. 8A illustrates another application of the conformal electrodeaccording to an embodiment of the present disclosure. FIGS. 8A-8Bdepicts conformal electrode array 200, left temporal horn 104, lefthippocampus 801, connector 206, and hermetically sealed package 703.Conformal electrode array 200 can be implanted in the temporal horn 104of the left lateral ventricle, for electrical recording from the lefthippocampus 801 from within the temporal horn 104. The electrode leadsfrom the entire array are bundled in connector 206, which exits theventricular system and the skull along the insertion path of thepreviously used endoscope. Connector 206 enters hermetically sealedpackage 703. Package 703 may be implanted between skull and scalp, andcontains implantable electronic elements for neural signal recording andwireless transmission. FIG. 8B illustrates the implanted system of 8A insagittal cross-section, seen from the left, indicating the positions ofconformal array 200 and hermetically sealed package 703.

Epilepsy often but not always arises due to lesions deep in the temporallobe that are difficult to access electrically and surgically. Medicallyrefractory epilepsy is a condition in which an individual is prone torecurrent seizures that cannot be controlled by antiseizure medications,though the individual may be otherwise neurologically normal betweenseizures. This class of seizure disorder is often caused by a lesiondeep within the temporal lobe of the brain (the associated condition isoften referred to as “mesial temporal lobe epilepsy”). Definitivetreatment for such lesions has traditionally involved major brainsurgery. In recent years, a variety of modern techniques have beendeveloped for ablating such lesions in minimally invasive fashion, oncea sufficiently high degree of diagnostic confidence is achieved withregard to lesion location. However, definitive diagnosis remainschallenging for the reasons described in the previous section: EEG, MEG,and ECoG provide limited spatial resolution when the lesions of interestare deep within the brain, and only a limited number of exploratorydepth electrodes can safely be placed.

Traditional, contemporary approaches to localizing seizure foci withinthe medial temporal lobe and hippocampus approach these structures fromthe external cortical surface. However, the surface of the medialtemporal lobe and hippocampus form the inner wall of the temporal hornof the lateral ventricle, and are therefore directly accessible toelectrode arrays placed within the cerebral ventricles. The systemdisclosed here provides for highly spatially accurate localization ofabnormal electrical activity in these deep structures, without requiringdepth electrodes or a traditional craniotomy (a conformal ventricularelectrode array can be introduced through a small burr hole, instereotactic or endoscope-assisted fashion).

One principal application of the conformal intraventricular electrodearray is in localization of seizure foci in patients having temporallobe epilepsy. In such patients, the electrode array is deployed inrecording mode, with electrodes arrayed along the ventricular surface ofthe temporal horn, which is defined by the structures of the medialtemporal lobe, including the hippocampus. In this application, the goalis precise spatial and anatomic localization of epileptogenic fociwithin the hippocampus or medial temporal lobe. The array configurationof the electrodes permits patterns of electrical activity to belocalized in three-dimensional space and correlated withthree-dimensional anatomic neuroimaging.

FIG. 9 shows detection of epileptogenic electrical activity using theconformal electrode array, in accordance with an embodiment of thepresent disclosure. FIG. 9 includes conformal electrode array 200,temporal horn 104, hippocampus 801, and an epileptogenic focus 901. Asshown in FIGS. 7 and 8A-8B, conformal array 200 is positioned adjacenthippocampus 801 of temporal horn 104. In this position, conformal array200 stimulates and detects epileptogenic electrical activity within thehippocampus in the temporal horn of the lateral ventricle. Thethree-dimensional distribution of electrodes enables a very precise andsensitive detection of electrical activity from a small epileptogenicfocus.

Neurologic disorders such as Parkinson's disease and epilepsy can betreated using spatially targeted electrical recording and stimulation ofspecific neuroanatomic structures. Electrical stimulation of deep braintargets is an important modality in the treatment of Parkinson'sdisease, essential tremor, and certain (thalamic) pain syndromes. Theefficacy of neuro stimulation-based therapy is highly dependent on theability to stimulate the correct target with precision. In certaincases, it is difficult or impossible to introduce a conventionalintraparenchymal depth electrode into the target without simultaneouslygenerating a lesion associated with electrode placement.

The conformal electrode array in the present disclosure can be used indeep brain stimulation for Parkinson's disease. A grid ofintraventricular electrodes enables highly versatile shaping ofelectrical fields, with the ability to design and modify the electricfield within and surrounding the traditional targets used during deepbrain stimulation. In some embodiments, the aggregate electric field andcurrent density function of the implanted array can be configured tostimulate deep brain nuclei associated with the treatment of Parkinson'sdisease and related movement disorders. These periventricular targetsinclude the subthalamic nucleus, globus pallidus, specific thalamicnuclei, and substantia nigra.

Other applications of the described conformal electrode array caninclude minimally invasive stimulation of the optic radiations. Thistechnique may provide an approach to delivering visual stimuli to theblind. Several approaches to electrical stimulation of the visualpathways have been experimentally demonstrated and reviewed (Pezaris etal. (2009) Neurosurg. Focus 27:E6), as potential approaches todeveloping a visual prosthesis for the blind. All such approaches, todate, have used intraparenchymal depth electrodes, which would requireintroducing lesions into the very tracts or grey matter structures thatcarry or process visual information, as the depth electrodes would needto penetrate the cortical regions or white matter tracts of interest.

Phosphenes, visual phenomena often described as transient “flashes oflight” related to electrical stimulation, are common side effects ofdeep brain stimulation during initial intraoperative placement andtesting of the electrodes, and subsequent programming. In the context ofdeep brain stimulation targeting the thalamus and subthalamic nucleus,for example, high-amplitude stimulation can give rise to fringeelectrical fields that cause depolarization of axons in the optictracts, giving rise to transient visual sensations. While these effectsare unwanted in the context of deep brain stimulation, they confirm thatit is possible to generate visual sensations in reproducible manner bycontrolling the electric field generated by electrodes placed at adistance from the optic pathway, rather than directly into the pathwayitself (at the level of the optic tracts, lateral geniculate nuclei,optic radiations, or visual cortex, for example).

The conformal array of intraventricular electrodes disclosed hereinenables highly versatile shaping of electrical fields, with the abilityto target locations along the visual pathway, including the optictracts, lateral geniculate nuclei, optic radiations, and visual cortex.An adaptive, computational approach to mapping the visual pathways usingelectrical stimulation and recording, with or without collaboration fromthe subject, holds promise for a prosthesis to restore vision to thevisually impaired.

Targeted electrical stimulation of white matter tracts transected byhemorrhage or stroke has the potential to restore neurologic function.Several approaches to electrical stimulation of the motor pathways havebeen experimentally demonstrated and reviewed, as potential approachesto developing a neural prostheses for paralyzed individuals and amputees(Wolpaw et al. (2012) Mayo Clin. Proc. 87:268-279), and as approaches torestoring function in patients paralyzed or partially paralyzed due tostroke (Boyd et al. (2015) Front Neurol. 6:226). Some such major andpromising approaches, to date, have used cortical surface electrodes orintraparenchymal depth electrodes, which can only be placed throughconventional neurosurgical techniques, and which can require introducinglesions into the very tracts that carry motor information, as theelectrodes need to penetrate the cortical regions or white matter tractsof interest.

Involuntary, stimulation-triggered muscular contractions are common sideeffects of deep brain stimulation during initial intraoperativeplacement and testing of the electrodes, and subsequent programming. Inthe context of deep brain stimulation targeting the thalamus or globuspallidus, for example, high-amplitude stimulation can give rise tofringe electrical fields that cause depolarization of axons in theinternal capsule, giving rise to transient muscular contractions (oftenin the face). While these effects are unwanted in the context of deepbrain stimulation, they confirm that it is possible to control motorfunction in reproducible ways by controlling the electric fieldgenerated by electrodes placed at a distance from the motor(corticospinal) tracts, rather than directly into the tracts themselves(at the level of the motor cortex or spinal cord).

The internal capsule is of particular interest in the context of thisdisclosure. Fibers of the internal capsule carry neural signalsregarding voluntary movement from the motor cortex to the spinal cord,from where they are transmitted to the skeletal muscles that generatesuch movement. The internal capsule is a common location for hemorrhagicstrokes, particularly those related to high blood pressure; strokes ofthis type tend to disrupt or destroy some of the internal capsulefibers, leaving stroke victims permanently weak or paralyzed on the sideof the body opposite the hemorrhage. Many of the internal capsule fiberstravel within millimeters of the ventricular surface, and are thereforeamenable to precise stimulation using precisely controlled electricalfields. This disclosure therefore has the potential to be used in thecontext of neural prosthetics for paralyzed and disabled individuals, aswell as for individuals recovering from stroke.

The conformal array of intraventricular electrodes disclosed herein canenable highly versatile shaping of electrical fields, with the abilityto target locations along the motor pathway, including multiple targetswithin the internal capsule. An adaptive, computational approach tomapping the motor pathways using electrical stimulation and recording,with or without collaboration from the subject, holds promise for aprosthesis to assist in restoring mobility and limb control to theparalyzed and disabled.

The conformal electrode array in the present disclosure can be used indeep brain stimulation for thalamic pain syndrome. In some embodiments,the aggregate electric field and current density function of theimplanted array is configured to stimulate targets within the thalamusassociated with thalamic pain syndrome.

The conformal electrode array in the present disclosure can be used forstimulation of hypothalamic nuclei. In some embodiments, the aggregateelectric field and current density function of the implanted array isconfigured to stimulate targets within specific nuclei of thehypothalamus, in the walls of the third ventricle. Such targeting may beuseful in the management of neuroendocrine disorders, circadian rhythmdisorders, physiologic responses to fever or hypothermia, and obesity,which are centrally physiologically regulated by specific nuclei in thehypothalamus.

The conformal electrode array in the present disclosure can be used instimulation of subcortical white matter tracts and internal capsule forstroke rehabilitation and neuromotor prostheses. In some embodiments,the aggregate electric field and current density function of theimplanted array can be configured to stimulate a set of targets withinthe motor pathways of the brain, including targets within the internalcapsule or cerebral or elsewhere in the corticospinal tract. In theseembodiments, the conformal electrode array can have clear advantagesover traditional depth and microelectrode arrays, as the conformal arraycan be configured to simulate the fields and current densities generatedby an array of electrodes implanted anywhere within large volumes of thebrain, without damaging or displacing brain tissue, and theconfiguration can be changed. Implanted electrodes or microelectrodearrays, by contrast, cannot easily be moved after implantation withoutrisk of significant brain injury. Furthermore, the set of targetsstimulated can be chosen in a three-dimensional manner that would bedifficult or impossible to achieve using any existing depth electrodesor microelectrode array. In some embodiments, feedback control based onsensed electrical activity within the sensory pathways, includingneuronal activity within the sensory thalamus, may be used to modulatemotor coordination.

The conformal electrode array in the present disclosure can be used instimulation of the sensory thalamus for neurosensory prostheses. Most ofthe surface of the thalamus is accessible from the ventricular system.Most of the major sensory pathways of the nervous system ascend throughthe brainstem and relay within the thalamus before ascending to thecortex. In some embodiments, the aggregate electric field and currentdensity function of the implanted array is configured to stimulate a setof targets within the sensory thalamus, for use in the context of asensory neuroprosthetic device, delivering sensory stimulation to thebrain (from modalities such as touch, pain, temperature, hearing, andvision) in a programmable manner, possibly based on data acquired byexternal sensors.

In some embodiments, the aggregate electric field and current densityfunction of the implanted array is configured to stimulate a set oftargets within the visual pathways of the brain, including targetswithin the optic tracts, lateral geniculate bodies, and opticradiations. In each of these targets, a topological representation ofimages projected on the retina is preserved in the organization ofneuronal cell layers and corresponding axons, facilitating rationalstimulation patterns intended to generate perception of meaningfulimages.

In these embodiments as well, the conformal array can be configured tosimulate the fields and current densities generated by multiple arraysof electrodes implanted at many sites within the optic pathways, withoutdamaging or displacing brain tissue in those pathways, and theconfiguration can be changed based on individual patient experience overtime. Implanted electrodes or microelectrode arrays, by contrast, cannoteasily be moved after implantation without risk of significant braininjury, and implantation would damage the optic pathways. Furthermore,the set of targets stimulated can be chosen in a three-dimensionalmanner that would be difficult or impossible to achieve using anyexisting depth electrodes or microelectrode array, anddifficult-to-access parts of the visual pathways can be targetednoninvasively.

In such visual prosthetic applications, stimulation could be deliveredin a programmed manner, based on data acquired by external sensors suchas video cameras.

While the disclosure has been described in connection with certainembodiments, it is to be understood that the disclosure is not to belimited to the disclosed embodiments but, on the contrary, is intendedto cover various modifications and equivalent arrangements includedwithin the spirit and scope of the disclosure, which scope is to beaccorded the broadest interpretation so as to encompass all suchmodifications and equivalent structures as is permitted under the law.

The invention claimed is:
 1. A method for electrically interacting witha neural tissue using an electrode array located within a ventricularcompartment of a brain, the method comprising: selecting a portion ofneural tissue for electrical interaction; accessing previously storedregistration information regarding a location of the electrode arraywithin the ventricular compartment of the brain; selecting one or moreelectrodes in the electrode array for electrical interaction based onthe registration information; and interacting with the neural tissuewith the selected electrodes, wherein interacting with the neural tissuecomprises at least one of forming an electrical field beam distributedin a three-dimensional space using the selected electrodes andlocalizing electrical activity in the brain using the selectedelectrodes distributed in the three-dimensional space.
 2. The method ofclaim 1, wherein interacting comprises stimulating neural activities ofthe neural tissue.
 3. The method of claim 1, wherein interactingcomprises recording neural activities of the neural tissue.
 4. Themethod of claim 1, wherein interacting comprises simultaneouslystimulating and recording neural activities of the neural tissue.
 5. Themethod of claim 1, wherein interacting comprises localizing electricalactivities from epileptogenic foci within a hippocampus for themanagement of epilepsy.
 6. The method of claim 5, wherein interactingcomprises stimulating the brain in response to epileptogenic activitywithin the hippocampus for the management of epilepsy.
 7. The method ofclaim 1, wherein interacting comprises interacting with motor pathwaysby an electrical field generated by the electrode array at a distance toassist in restoring mobility and limb control.
 8. The method of claim 1,wherein interacting comprises stimulating visual pathways to generatevisual perception.
 9. The method of claim 1, wherein interactingcomprises stimulating sensory cortex or sensory thalamus to deliversensory stimulation to the brain for a neurosensory prosthesis or forthe treatment of thalamic pain.
 10. The method of claim 1, whereininteracting comprises stimulating hypothalamic nuclei for the managementof neuroendocrine disorders, circadian rhythm disorders, physiologicresponses to fever or hypothermia, or obesity.
 11. The method of claim1, comprising registering the electrode array to obtain its orientationand position within the ventricular compartment of a brain.
 12. Themethod of claim 11, comprising registering the electrode array vianeuroimaging.
 13. The method of claim 1, comprising placing theelectrode array into the ventricular compartment of a brain via aminimally invasive insertion technique.
 14. The method of claim 13,comprising placing the electrode array into the ventricular compartmentof a brain via a cannula or catheter.